Cytoskeleton and Signaling Pathways in Photoreceptors

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Photoreceptors have complex cytoskeletons that may regulate morphogenesis of light sensitive organelles and certainly direct protein and vesicular trafficking. Signaling pathways that control cytoskeletal organization in other cells have been identified. In photoreceptors, the best known signaling pathway is phototransduction involving the G-protein coupled receptor rhodopsin. We believe that the absorption of light by rhodopsin affects other signal transduction pathways, which run in parallel with phototransduction, and lead to morphological changes in photoreceptors and relocation of retinal proteins that have been described. Furthermore, we believe that these observed changes are directed by the cytoskeleton whose organization is controlled by signaling pathways switched on and off by rhodopsin function. We think that Rho GTPase signaling pathways are affected by rhodopsin activity and control the overall organization of the cytoskeleton in photoreceptors; that activation of rhodopsin recruits signaling pathways leading to changes in mRNA expression of cytoskeletal proteins and other proteins that may interact with the cytoskeleton; and that mRNA for some of these cytoskeletal proteins is stored and translated when needed in either the light or dark. To test our assumptions we will pursue the following Specific Aims: 1) light regulates a Rho signaling pathway in photoreceptors that affects actin distribution; 2) light regulates the expression of specific cytoskeletal mRNAs in photoreceptors and their translation into protein; and 3) specific cytoskeletal mRNAs in photoreceptors are dormant until translation in the appropriate lighting condition. Our model system will be octopus photoreceptors which are large and easy to manipulate and facilitate immunocytochemical, molecular and biochemical studies aimed at elucidating the effects of light on retinal cytoskeletal organization. We have preliminary evidence to support the pursuit of each specific aim and their completion will significantly advance our understanding of how light affects cytoskeletal organization and gene expression photoreceptors and to the understanding of molecular pathways that control this organization. Knowledge of retinal signaling pathways will facilitate our understanding of retinal diseases that involve cytoskeletal proteins.